Oxytocin Stimulates the Release of Luteinizing Hormone-Releasing Hormone from Medial Basal Hypothalamic Explants by Releasing Nitric Oxide

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-03, Vol.94 (6), p.2741-2744
• Main Authors: Rettori, V., Canteros, G., Renoso, R., Gimeno, M., McCann, S. M.
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Animal behavior; Animal reproduction; Animals; Biological Sciences; Dinoprostone - metabolism; Enzymes; Gonadotropin-Releasing Hormone - metabolism; Hemoglobins; Hemoglobins - pharmacology; Hormones; Hypothalamus; Hypothalamus, Middle - drug effects; Hypothalamus, Middle - physiology; Kinetics; Luteinization; Male; Mating behavior; Models, Neurological; Neurons; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitroprusside - pharmacology; Norepinephrine; omega-N-Methylarginine - pharmacology; Organ Culture Techniques; Oxides; Oxytocin - metabolism; Oxytocin - pharmacology; Pituitary Gland, Posterior - drug effects; Pituitary Gland, Posterior - metabolism; Rats; Rats, Wistar; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.6.2741

Oxytocin induces mating behavior in rats of both sexes. Previous experiments revealed that progesterone-induced sex behavior in ovariectomized, extrogen-primed rats was caused by release of NO from NOergic neurons that stimulated the release of luteinizing hormone-releasing hormone (LHRH). The LHRH activated brain-stem neurons that initiated the lordosis reflex. We hypothesized that oxytocin might similarly release NO in the medial basal hypothalamic region that would stimulate release of LHRH into the hypophyseal portal vessels to release luteinizing hormone. To investigate this hypothesis, medial basal hypothalamic explants were preincubated in Krebs--Ringer bicarbonate buffer for 30 min, followed by a 30-min incubation in fresh Krebs--Ringer bicarbonate buffer containing the compounds to be tested. Oxytocin stimulated LHRH release 3- to 4-fold at the lowest concentration tested (10-10M). Values remained at a plateau as the concentration was increased to 10-7M and then declined in a concentration-dependent manner, so that there was no stimulation with a concentration of 10-5M. Oxytocin (10-7M) stimulated release of prostaglandin E2into the medium, a finding consistent with a role of NO in the response. That NO indeed mediated the action of oxytocin was supported by blockade of the action of oxytocin by the competitive inhibitor of NO synthase (NOS), NG-monomethyl-L-arginine (300 μ M). Furthermore, oxytocin (10-9to 10-7M) activated NOS as measured at the end of the experiments. Oxytocin appeared to act to stimulate norepinephrine terminals in the medial basal hypothalamus, which activated NOS by α1-adrenergic receptors, because prazocine, an α1receptor blocker, inhibited the LHRH-releasing action of oxytocin. Finally, incubation of neural lobe explants with sodium nitroprusside, a NO releasor, revealed that nitroprusside (300-600 μ M, but not 900 μ M) inhibited oxytocin release. Therefore, the NO released by oxytocin also diffuses into the oxytocin neuronal endings and inhibits oxytocin release, forming a negative feedback loop. The results indicate that oxytocin is important not only in induction of mating, but also in stimulating LHRH release with subsequent luteinizing hormone discharge that plays a crucial role in reproduction.